Field
The subject matter provided herein relates to inhibition of p67phox protein; in particular compounds, compositions and methods relating to inhibition of p67phox protein.
Description of the Related Technology
The multicomponent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase NOX2 enzyme complex facilitates the production of reactive oxygen species (ROS) to mediate innate immunity. NADPH oxidase-dependent processes occur in many different cell types for both host defense and intracellular signal transduction. Inappropriate regulation of the NADPH oxidase complex has been proposed to contribute to a multitude of inflammation-mediated disorders. Biochemical studies have identified a molecular mechanism of NOX2 regulation; its activation is dependent on a series of protein interactions that are initiated in the cytoplasm and translocate to the cell membrane for full NADPH oxidase complex activation. In response to inflammatory stimuli, four cytosolic proteins in the “regulatory complex,” that is, Rac1/2, p47phox, p67phox and p40phox, are translocated to the membrane, where they interact with the plasma membrane-bound NOX2 and p22phox subunits. One limiting step in the assembly of this active NADPH oxidase complex is the binding of p67phox to the activated, GTP-bound Rac1 and/or Rac2. The binding of p67phox to Rac1/2-GTP allows for the complete assembly of the complex and activation of NOX2 NADPH oxidase.